Human metapneumovirus (hMPV) is a newly discovered respiratory virus and may be an unrecognized cause of serious respiratory illness in elderly adults. Our preliminary data suggests that hMPV may account for a substantial number of hospitalizations in this age group, and therefore is deserving of in depth study, possibly with efforts toward vaccine development. At present there is little available information about the epidemiology and clinical impact of hMPV in adult age groups. As a first step towards a better understanding of the importance of hMPV in adult populations, serum samples, nasal secretion specimens and clinical data from a recently completed 4-year prospective surveillance study of respiratory infections in several cohorts of adults will be analyzed for hMPV. We have developed sensitive and specific real time RT-PCR as well as serum enzyme immunoassay (ElA) for diagnosis of hMPV. Overall, 1575 young adults, healthy elderly, high-risk adults and residents of long term care facilities were followed during a 4 year period from 1999 - 2003. These subjects had 1428 illnesses evaluated, of which 95% are available for hMPV analysis. In addition, 1330 hospitalized subjects were evaluated during this period. Overall, 214 influenza A and 294 RSV infections were identified. Pre- and post-season sera from prospective cohorts and acute and convalescent sera from all illnesses will be analyzed for hMPV infection using an EIA. All nasal secretions from acute illnesses will be tested for hMPV by RT-PCR. The incidence of symptomatic and asymptomatic hMPV infection will be calculated and compared with influenza and RSV infections identified in these subjects during the same period. The clinical characteristics, including clinical impact, of hMPV illnesses in each of the adult subgroups will be analyzed and compared with RSV and influenza. hMPV will be identified as group A or B by strain specific RT-PCR and the epidemiology and clinical impact of each virus strain will be described. In addition to determining the incidence and impact of hMPV in adult populations we will analyze the role of serum and mucosal antibodies in protection from hMPV infection and severe disease. Monoclonal antibodies (Mabs) to HMPV will be generated to facilitate development of a serum micro neutralization assay for the study of functional antibody. This study will provide data that will be useful in determining the need for and design of future larger scale prospective studies of HMPV in the elderly as well as the feasibility of vaccines based on stimulating humeral immunity.